The proposed project is directed towards an evaluation of erythropoiesis in neoplastic disorders. The studies include: 1) assay of serum and urinary erythropoietin in patients with anemia associated with cancer; 2) evaluation of the proliferative characteristics of erythroid progenitor cells in these disorders; 3) determination of the role of humoral inhibitors of erythropoiesis in the generation of these anemias; 4) separation of the bone marrow erythroid precursor cells from tumor cells and determination of the effect of the interaction of those fractions on erythropoiesis; 5) by co-cultivation studies, determination of the role of lymphocyte or macrophage mediated suppression of erythropoiesis in the generation of anemia in these patients; 6) establishment of short-term cultures of tumor cells and assays of their supernatants for erythropoiesis inhibitory activity; 7) co-cultivation of tumor cells with normal bone narrow to determine the importance of tumor cell-erythroid progenitor cell relationships in production of anemia; 8) in vitro exposure of normal macrophages to tumor cells and determination of their effect on erythroid colony growth of normal human marrow. These studies should lead to a better understanding of the mechanisms underlying the anemia of cancer and significantly improve our approach to therapy in these patients.